Pregnancy-Induced Thrombocytopenia in Pseudo-Von Willebrand Disease

Abstract 4658

Platelet-type von Willebrand disease, or pseudo-VWD, is a rare congenital platelet disorder due to a mutation in the glycoprotein 1b alpha receptor. This results in increased binding of normal VWF to platelets, leading to platelet aggregation and intermittent thrombocytopenia. Although the mechanism is similar to type IIb VWD, this gain of function mutation affects the platelet, rather than plasma VWF.

We report a patient with pseudo-VWD who developed progressive thrombocytopenia during pregnancy. She was initially seen at 10 weeks gestation, when the platelet count was 143 × 10⁹ /L (figure 1). As the pregnancy progressed, the platelet count decreased, accompanied by an inverse rise in VWF antigen and activity, factor VIII activity, and an increase in high molecular weight (HMW) multimers (figure 2). The VWF activity to antigen ratio remained abnormal at all times. At the time of delivery, the platelet count reached a nadir of 36 × 10⁹/L. Post-partum, the platelet count normalized to 185 × 10⁹/L with a concomitant fall in VWF antigen and activity levels. VWF multimer analysis after delivery showed an absence of high molecular weight multimers.

FIGURE 1

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FIGURE 1

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FIGURE 2

Weeks Gestation .	Platelet count (×109 /L) .	VWF antigen .	VWF activity .	Factor VIII .	Platelet aggregation .	VWF multimers .
10	143	81%	35%	88%	↑ ristocetin 0.6	normal
36	54	144%	57%	205%	not done	normal
+15 post-partum	185	55%	19%	49%	not done	HMW multimers absent

Weeks Gestation .	Platelet count (×109 /L) .	VWF antigen .	VWF activity .	Factor VIII .	Platelet aggregation .	VWF multimers .
10	143	81%	35%	88%	↑ ristocetin 0.6	normal
36	54	144%	57%	205%	not done	normal
+15 post-partum	185	55%	19%	49%	not done	HMW multimers absent

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The likely etiology of the progressive decrease in the platelet count is secondary to the physiologically stimulated rise in VWF levels during pregnancy. With rising VWF levels, the abnormal platelet GP1b alpha receptor binds VWF, resulting in platelet-VWF aggregates with subsequent clearance. Transfusion of normal platelets would be the only way to correct the abnormality. Our patient, a Jehovah's Witness, would not accept platelet transfusion if it became necessary. She underwent an uncomplicated cesarean section for obstetric indications.

Our patient's family was the subject of the landmark article initially describing this condition (Weiss HJ, Meyer D, Rabinowitz R, et al. Pseudo- von Willebrand's disease: An intrinsic platelet defect with aggregation by unmodified human factor VIII/von Willebrand factor and enhanced adsorption of its high-molecular-weight multimers. N Engl J Med 1982; 306:326-333). This patient is the 2-year old who was not tested when the family was initially evaluated. To our knowledge, this is the first reported case of pregnancy-associated thrombocytopenia in a patient with pseudo-VWD.